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Co-aggregation and heritability of organ-specific autoimmunity: a population-based twin study
Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden; Department of Medicine, Karlstad Central Hospital, Karlstad, Sweden.
Center for Molecular Medicine, Department of Medicine (Solna), Karolinska Institutet, Stockholm, Sweden; Department of Endocrinology, Inflammation and Infection Theme, Karolinska University Hospital, Stockholm, Sweden.
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
Department of Surgical Sciences, Uppsala University, Uppsala, Sweden.
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2020 (English)In: European Journal of Endocrinology, ISSN 0804-4643, E-ISSN 1479-683X, Vol. 182, no 5, p. 473-480Article in journal (Refereed) Published
Abstract [en]

Objective: Co-aggregation of autoimmune diseases is common, suggesting partly shared etiologies. Genetic factors are believed to be important, but objective measures of environ mental vs heritable influences on co-aggregation are absent. With a novel approach to twin studies, we aimed at estimating heritability and genetic overlap in seven organspecific autoimmune diseases.

Design: Prospective twin cohort study.

Methods: We used a cohort of 110 814 twins to examine co-aggregation and heritability of Hashimoto's thyroiditis, atrophic gastritis, celiac disease, Graves' disease, type 1 diabetes, vitiligo and Addison's disease. Hazard ratios (HR) were calculated for twins developing the same or different disease as compared to their co-twin. The differences between monozygotic and dizygotic twin pairs were used to estimate the genetic influence on co-aggregation. Heritability for individual disorders was calculated using structural equational modeling adjusting for censoring and truncation of data.

Results: Co-aggregation was more pronounced in monozygotic twins (media n HR: 3.2, range: 2.2-9.2) than in dizygotic twins (median HR: 2.4, range: 1.1-10.0). Heritability was moderate for atrophic gastritis (0.38, 95% CI: 0.23-0.53) but high for all other diseases, ranging from 0.60 (95% CI: 0.49-0. 71) for Graves' disease to 0.97 (95% CI: 0.91- 1.00) for Addison's disease.

Conclusions: Overall, co-aggregation was more pronounced in monozygotic than in dizygotic twins, suggesting that disease overlap is largely attributable to genetic factors. Co-aggregation was common, and twins faced up to a ten-fold risk of developing diseases not present in their co-twin. Our results validate and refine previous heritability estimates based on smaller twin cohorts.

Place, publisher, year, edition, pages
Bioscientifica, 2020. Vol. 182, no 5, p. 473-480
National Category
Endocrinology and Diabetes
Identifiers
URN: urn:nbn:se:oru:diva-81794DOI: 10.1530/EJE-20-0049ISI: 000528194900006PubMedID: 32229696Scopus ID: 2-s2.0-85082790635OAI: oai:DiVA.org:oru-81794DiVA, id: diva2:1429662
Funder
Stockholm County CouncilSwedish Society for Medical Research (SSMF)Åke Wiberg FoundationSwedish Research CouncilNovo Nordisk
Note

Funding Agency:

County Council of Värmland

Available from: 2020-05-12 Created: 2020-05-12 Last updated: 2020-12-01Bibliographically approved

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Ludvigsson, Jonas F.

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